Summary: Research in the Interventional Radiology (IR) lab is motivated by the fact that image guidance and minimally invasive approaches have revolutionized the management of many common diseases. However, diagnosis and therapy remain distinctly separated from each other in both time and space. We believe that this gap between diagnosis and therapy can be narrowed by minimally invasive image guided therapies and with the application of novel guidance technologies and engineered vectors. All research efforts in the IR lab are developed with a clear translational route to the clinic and address areas of urgent clinical need. The IR labs research program is separated into three main areas: electromagnetic (EM) and optical tracking and robotics, drug + device combinations, novel methods of augmentation of ablative energies (RFA or HIFU). The diversity of these projects requires an interdisciplinary team of researchers and takes full advantage of the interdisciplinary resources found within the Clinical Center and the Intramural Research Program of the National Institutes of Health. We believe that combining the imaging tools inherent to interventional radiology with pharmaceuticals and medical devices can make a significant contribution to the future treatment of both localized and systemic diseases, with an emphasis upon cancer therapeutics. Principal projects are: 1) Smart biopsy, 2) OR of the future and, 3) Drugs + devices. Smart biopsy relies upon precise electromagnetic tracking to target tissue to correlate sample with imaging parameters. OR of the future is a broad translational project that integrates a variety of technologies for navigation, automation, and visualization of medical procedures. Sub-projects within the Drug + Device model include: 1) Temperature sensitive liposomes combined with radiofrequency ablation (RFA) or high intensity focused ultrasound (HIFU), 2) Radiofrequency ablation combined with antiangiogenic therapy, and 3) Development of image-able drug eluting beads (DEB) for transcatheter arterial chemoembolization (TACE). The clinical treatment of solid tumors could be improved by controlling the pharmacologic properties of anticancer therapeutics to deliver a greater dose to the tumor; with conventional drugs, this dose is typically limited by toxic side effects in normal tissues. Therefore, the efficacy of current anticancer treatments may be improved with advances in drug delivery technologies that have received increased attention in recent years. The goal of drug delivery in the treatment of cancer is to increase the concentration of a therapeutic agent in the tumor while limiting systemic exposure and subsequent normal tissue toxicity. The combination of drug delivery technologies with image guided interventions represents a rich field with great translational potential and the ability to bridge the gap between diagnosis and therapy. Diagnosis and therapy remain distinctly separated from each other in time and space. The gap between diagnosis and therapy can be closed by minimally invasive image guided therapies. Real-time, intra-procedural tools will blend diagnosis and therapy into a dynamic, iterative process with improved outcomes. The redefining of surgical-like procedures will be fueled by multi-modality imaging, navigation, visualization, robotics, and automated precision tools. These enabling technologies have not yet been optimally applied to existing clinical problems, especially in minimally-invasive image guided therapies. This presents an opportunity to integrate these technologies into the clinical setting in a validated and cost-effective manner, and to study the impact prior to broad implementation. Image guidance and multimodality navigation will fuel a small revolution in procedural medicine, which presents unprecedented opportunity and challenge. Image guidance and minimally invasive approaches have revolutionized themanagement of many common diseases. The miniaturization of surgical interventions has seen the broad adoption of needle or catheter-based procedures such as tumor embolization, brain aneurysm coiling, aortic stent grafting, uterine fibroid embolization, atherosclerosis stenting and angioplasty, and tumor thermal ablation with radiofrequency. As procedures are becoming less and less invasive, they are more and more targeted and guided by imaging and spatial information. The ability to navigate a medical device to a target based upon multiple windows or multiple modalities should have tremendous advantages in certain settings. The combination of functional and morphologic (metabolic and anatomic) information on the same coordinate system is empowering. With multiple public and private partners, we have developed a multimodality interventional radiology suite that uses a CT coordinate frame to co-register different devices including pre-procedural images, intra-procedural ultrasound, CT, rotational fluoroscopy, robotics, electromagnetic tracking and therapeutic ultrasound, microwave, radiofrequency, etc. to allow the best combinations of techniques and guidance methods tailored to the particular patients needs. Combining imaging modalities can take advantage of each modality's strength. Real-time feedback and temporal resolution of ultrasound can be combined with the functional and metabolic data from PET and the spatial resolution of MR or CT, all on one seamless platform for treatment planning, targeting, procedural navigation, monitoring, and verification of treatment.The lab has continued the electromagnetic tracking clinical trial and further studied Medical GPS for tumor ablation and treatment planning, and for prostate biopsies using MRI information, but not requiring an MRI to be physically present. This fiscal year, a clinical trial comparing cone beam CT (CBCT) navigation to conventional imaging (CT) and EM tracking during image guided procedures (11-CC-0082) was continued, CBCT with fusion PET guidance was continued, laser ablation of prostate cancer under MRI guidance was continued, Laser and block guidance for needle based biopsy and ablation were continued, and CBCT for bronchoscopy was planned. Preclinical work is in process for focal prostate therapies (heat deployed drugs for focal prostate cancer) and preclinical studies are under way for thoracic aortic stent grafts. Developments in navigation have allowed a clinical trial to be designed that will study angle selection techniques and assess accuracy of CT integrated robot-like devices (10-CC-0217). Preclinical work on RFA plus anti-angiogenic agents was completed in part and is moving towards clinical trials. Drug eluting beads as a tool for regional therapies is being refined in the preclinical models, and a clinical trial for irinotecan drug eluting beads has been initiated and is currently recruiting patients (11-CC-0131). Image-able drug eluting beads have been studied for conspicuity in the lab and in vivo settings. Preclinical studies for navigation in endobronchial steerable catheters will soon be translated to patients as well. Navigation tools for open and laparoscopic surgery are being developed. Devices have been developed for IVC filters, catheters to inhibit bacterial colonization, and endovascular devices for vessel embolization. Surgical navigation devices were planned and prototyped.